title: Alpha-mercaptoketone based histone deacetylase inhibitors.
abstract: In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.
authors.affiliation: Department of Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Wash
authors.forename: Timothy Z
authors.initials: TZ
authors.lastname: Hoffman
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Wiley
authors.forename: Céline
authors.initials: C
authors.lastname: Bonnefous
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Smith
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sertic
authors.forename: Charles M
authors.initials: CM
authors.lastname: Lawrence
authors.forename: Kent T
authors.initials: KT
authors.lastname: Symons
authors.forename: Phan-Manh
authors.initials: PM
authors.lastname: Nguyen
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Lustig
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Tami
authors.initials: T
authors.lastname: Annable
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Noble
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Hager
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hassig
authors.forename: James W
authors.initials: JW
authors.lastname: Malecha
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002614:Chelating Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000737:chemistry; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007659:Ketones; D011355:Prodrugs; D015032:Zinc